Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody.

Abstract

BACKGROUND:

Production of high levels of IL-6 is often correlated with resistance to cytotoxics or ionizing radiations, in cancer cell lines as in various cancer patients. We investigated whether monoclonal antibodies directed against IL-6 may enable to reverse resistance of cancer cell lines.

METHODOLOGY/PRINCIPAL FINDINGS:

We exposed ten haematological cancer cells from lymphoma, myeloma, or leukemia origins to cytotoxics or ionizing radiations and assessed the effects of anti-IL-6 antibody addition on cell proliferation, apoptosis, or IL-6 signaling. A strong correlation between IL-6 secretion, measured by ELISA, and resistance to doxorubicin as ionizing radiations was observed in the multiple myeloma U266 and the Burkitt's lymphoma Daudi and Namalwa cells. Although an anti-IL-6 antibody combined to both treatments efficiently blocked IL-6 signaling in U266 cells, expressing the IL-6 receptor gp80, it did not increase treatment-induced anti-proliferative and pro-apoptotic effects on these cells, as well as on Daudi and Namalwa cells. This lack of effect could be related to diverse factors: 1) a higher release of the soluble form of IL-6 receptor gp80 in response to doxorubicin and irradiation from all cell lines, 2) an impaired level of the IL-6 pathway inhibitor SOCS3 in Daudi cells, and 3) an increased release of IL-10 and TNFalpha, two cytokines involved in cell radio- and chemoresistance.

CONCLUSIONS/SIGNIFICANCE:

These data support the fact that IL-6 is not the preponderant actor of cell resistance to cytotoxics and ionizing radiations, which seems to be regulated by a complex network of proteins.

• Authors: Angélique Gougelet, Adeline Mansuy, Jean-Yves Blay, Laurent Alberti, Claudine Vermot-Desroches
• Journal: PloS one (PLoS One) Vol. 4 Issue 11 Pg. e8026 (Nov 30 2009) ISSN: 1932-6203 [Electronic] United States
• PMID: 19956602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contactins
• Interleukin-6
• Neural Cell Adhesion Molecules
• Receptors, Interleukin-6
• SOCS3 protein, human
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Tumor Necrosis Factor-alpha
• interleukin-6 receptor alpha
• Interleukin-10
• Doxorubicin

Topics

• Cell Line, Tumor
• Contactins
• Doxorubicin (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Interleukin-10 (chemistry)
• Interleukin-6 (chemistry, immunology, metabolism)
• Lymphoma (drug therapy, metabolism, radiotherapy)
• Multiple Myeloma (drug therapy, metabolism, radiotherapy)
• Neural Cell Adhesion Molecules (metabolism)
• Radiation, Ionizing
• Receptors, Interleukin-6 (chemistry, metabolism)
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (metabolism)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)